- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01189097
Combined Therapy of Methadone and Dextromethrophan (DM)
Combined Therapy of Methadone and Dextromethrophan: A Novel Strategy for the Treatment of Opioid Dependence
The purpose of this study is to determine the pharmacological effects and outcomes of DM therapy with this add-on study.
And to determine the immunological changes between the baseline and the end point of the study.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Opioid dependence is a severe public health problem. Current efforts to taper individuals off opioid medications are limited due to a high relapse rate and lack of efficacy in relieving subjective symptoms. Methadone substitution therapies might decrease the criminal rate and increase the quality of life for individuals with opioid dependence, but the high drop-out rate and continuing use of methadone are major problems in the maintenance of therapy for opioid dependence. Studies in the pathogenesis of opioid dependence and additional behaviors need more focused attention.
Dextromethorphan (DM) is a noncompetitive N-methyl-D-aspartate receptor antagonist that has proven safety record for anti-tussive purpose. Previous studies demonstrated that DM may be useful in decreasing craving in animals (Huang, et al., 2003; Lue et al., 2007) and withdrawal tendencies in human with opioid dependence. In recent studies, DM has been reported to afford neuroprotection against endotoxin-induced dopaminergic neurotoxicity (Li et al. 2005; Liu et al. 2003; Zhang et al. 2004, 2005) which might be related to treatment for additictive behaviors. The purposes of this study are to examine whether DM is able to 1) reduce opioid tolerance and decrease methadone use; 2) reduce withdrawal symptoms; 3) decrease the relapse rate of opioid use, and 4) be an effective treatment for opioid dependence (and addictive behaviors).
This is a double-blinded, placebo-controlled, randomized, and parallel groups clinical research trial study. Subjects with opioid dependence are recruited from two different sources. One group will come from the list of current opioid users and will be required to stay on methadone treatment (opioid using group), and the second group will come from subjects who are forced to discontinue opioid use for more than one week (opioid free group).
In the opioid using group, add-on of DM or placebo treatment will proceed in a double-blind fashion for 12 weeks after completed structured diagnostic interview and adjusted methadone dose. In the opioid free group, subjects will take one-week placebo for the wash-out period first and then will be admitted into a double-blind DM/placebo only for 12 weeks. Both opioid using and opioid free groups will be examined weekly through urine tests for opioid use and will be assessed on a craving scale after the completion of the structured diagnostic interviews. We will measure the treatment response and side effects to clarify the curative effects of DM with the use of the double-blinded DM/placebo therapy design in both the opioid using and opioid free groups. Several psychological examinations, psychosocial questionnaires, tests for immune parameters, electrophysiological studies and genetic markers will be performed in this study. The interim analysis and decording of partial subjects who completed DM/placebo add-on treatment for three months will be performed in the end of first year.
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Tainan, Taiwan, 704
- Recruiting
- Ru-Band Lu
-
Contact:
- Ru-Band Lu, MD
- Phone Number: 5108 +886-6-2353535
- Email: rblu@mail.ncku.edu.tw
-
Principal Investigator:
- Ru-Band Lu, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Signed informed consent by patient or legal representative.
- Male or female patient aged ≧18 and ≦65 years.
- A diagnosis of opioid dependence according to DSM-IV criteria made by a specialist in psychiatry.
- Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study.
Exclusion Criteria:
- Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study.
- Females who are pregnant or nursing.
- Patient has received DM or other anti-inflammatory medications within 1 week prior to the first dose of the double-blinded medication.
- Other major Axis-I DSM-IV diagnosis other than opioid dependence such as multiple substance dependence within 1 year prior to the fist dose of the double-blinded medication.
- Current evidence of an uncontrolled and/or clinically significant medical condition, e.g., cardiac, hepatic and renal failure that would compromise patient safety or preclude study participation.
- History of intolerance to methadone or DM.
- History of sensitivity reaction (e.g., urticaria, angioedema, bronchospasm, severe rhinitis, anaphylactic shock) to DM.
- Patient has received electroconvulsive therapy (ECT) within 4 weeks prior to the first dose of the double-blinded medication.
- Increase in total SGOT, SGPT, gamma-GT, BUN and creatinine by more than 3X ULN (upper limit of normal).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: dextromethorphan
|
Subjects who have not used opioid for at least one week before baseline evaluation will take one-week placebo for the wash-out period first and then will be categorized into the opioid free group.
The subjects of the opioid using group will be assigned randomly into the following six groups: 1) Methadone + DM 60mg; 2) Methadone + DM 120mg; 3) Methadone + Placebo; 4) Methadone + DM 60mg + motivation and cognitive behavior therapy; 5) Methadone + DM 120mg + motivation and cognitive behavior therapy; 6) Methadone + Placebo + motivation and cognitive behavior therapy.
The opioid free group will be 1) DM 30mg; 2) DM 60 mg; 3) Placebo.
Subjects who have not used opioid for at least one week before baseline evaluation will take one-week placebo for the wash-out period and then randomly assigned into six groups: 1) Methadone + DM 60mg; 2) Methadone + DM 120mg; 3) Methadone + Placebo; 4) Methadone + DM 60mg + motivation and cognitive behavior therapy; 5) Methadone + DM 120mg + motivation and cognitive behavior therapy; 6) Methadone + Placebo + motivation and cognitive behavior therapy.
The opioid free group will be 1) DM 30mg; 2) DM 60 mg; 3) Placebo.
If the subjects of the opioid free group suffer from relapses and begin to use heroin, they will receive methadone treatment.
The dosage of methadone will be increased or decreased maximal 5 mg each time as necessary.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Urinary examination
Time Frame: baseline
|
Using urinary examination is aimed to test whether the drug dependence is still using morphine or not.
|
baseline
|
Urinary examination
Time Frame: week 1
|
Using urinary examination is aimed to test whether the drug dependence is still using morphine or not.
|
week 1
|
Urinary examination
Time Frame: week2
|
Using urinary examination is aimed to test whether the drug dependence is still using morphine or not.
|
week2
|
Urinary examination
Time Frame: week4
|
Using urinary examination is aimed to test whether the drug dependence is still using morphine or not.
|
week4
|
Urinary examination
Time Frame: week8
|
Using urinary examination is aimed to test whether the drug dependence is still using morphine or not.
|
week8
|
Urinary examination
Time Frame: week12
|
Using urinary examination is aimed to test whether the drug dependence is still using morphine or not.
|
week12
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
cytokines
Time Frame: baseline
|
baseline
|
cytokines
Time Frame: week1
|
week1
|
cytokines
Time Frame: week2
|
week2
|
cytokines
Time Frame: week4
|
week4
|
cytokines
Time Frame: week8
|
week8
|
cytokines
Time Frame: week12
|
week12
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Narcotic-Related Disorders
- Opioid-Related Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Respiratory System Agents
- Antitussive Agents
- Dextromethorphan
Other Study ID Numbers
- HR-95-139
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Opioid Abuse
-
Baylor College of MedicineChandrakantanWithdrawnOpioid Dependence | Opioid Use | Opioid Abuse, Unspecified
-
Bubba NicholsonTampa General Hospital; Otrimed Clinical ResearchUnknownOpioid-Related Disorders | Opioid Dependence | Opioid Use | Opioid Abuse | Opioid-use Disorder | Opioid Addiction | Opioid Intoxication | Opioid Abuse, Continuous Use | Paternal Pheromone Deficiency | Opioid Abuse, Episodic
-
The University of Texas Health Science Center at...TerminatedOpioid Dependence | Opioid Abuse, UnspecifiedUnited States
-
Weill Medical College of Cornell UniversityThe Institute for Family Health; New York State Health FoundationCompletedOpioid-Related Disorders | Opioid Use | Opioid Abuse | Prescription Drug Abuse and DependencyUnited States
-
Kaiser PermanenteNational Institute on Drug Abuse (NIDA)Active, not recruitingOpioid Use Disorder | Substance Use Disorders | Substance Abuse | Opioid Abuse | Drug Abuse | Drug Use Disorders | Cannabis Abuse | Cannabis-Related Disorder
-
University of North Carolina, Chapel HillNational Institute on Drug Abuse (NIDA)CompletedOpioid Abuse (Disorder)United States
-
Rutgers, The State University of New JerseyNational Institute on Drug Abuse (NIDA); University of UtahRecruitingTobacco Use | Opioid Use | Polysubstance AbuseUnited States
-
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUnknownOpioid Abuse or Dependence
-
Wayne State UniversityHenry Ford Health SystemRecruitingOpioid Abuse | Benzodiazepine Abuse | Polysubstance AbuseUnited States
-
University of UtahNational Institute on Drug Abuse (NIDA); University of CincinnatiNot yet recruitingOpioid Abuse | Prescription Opioid AbuseUnited States
Clinical Trials on Dextromethorphan
-
Boehringer IngelheimCompleted
-
PfizerCompletedHealthy VolunteersBelgium
-
National Institute of Neurological Disorders and...CompletedParkinson's Disease | Neurodegenerative DiseaseUnited States
-
National Institute of Dental and Craniofacial Research...CompletedDiabetic Neuropathies | Neuralgia | Herpes ZosterUnited States
-
PfizerMedivation, Inc.CompletedAlzheimer Disease | Huntington DiseaseUnited States
-
Hugo W. Moser Research Institute at Kennedy Krieger...The Johns Hopkins Institute for Clinical and Translational Research (ICTR)CompletedRett SyndromeUnited States
-
National Institute on Drug Abuse (NIDA)Unknown
-
University of Medicine and Dentistry of New JerseyNational Cancer Institute (NCI)TerminatedUnspecified Childhood Solid Tumor, Protocol Specific | Fatigue | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Medical University of South CarolinaCompletedMajor Depressive Disorder